Hypoxia during critical developmental stages in the perinatal period is suspected of being an important source of human morbidity. Inadequate oxygenation, if prolonged, may cause maturation defects, many of which involve the nervous system primarily. This proposal deals with an animal model of the effects of perinatal hypoxia. Rats reared in circumstances of chronic subacute, and acute hypoxia will be sacrificed at specified ages for electrophysiological, biochemical, and morphological analyses. The dentate gyrus of the hippocampal formation will be singled out for an extensive study of the effects of hypoxia. In rats and other mammals dentate neurons and fiber pathways continue to mature anatomically for several weeks into postnatal life. The effects of hypoxia will be studied on orderly maturation as observed in light microscopy, and on neurotransmitter concentrations as determined by assay. Information on changes in bioelectric responsiveness will be obtained from microiontophoretic application of suspected transmitters and related conpounds, and field potentials in response to electrical stimuli through known synaptic pathways. The hypothesis is that a subtle change in electrical responsiveness may be the earliest indicator of damage to the system. The experiments are designed to give quantitative information in dose-response and time-action form on the effects of hypoxia in an animal model. With this information it might be possible to develop lines of clinical research which could lead to rational early treatment strategies for subjects at risk because of perinatal hypoxic episodes.